Abstract
BackgroundPlasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of malaria remain elusive.MethodsThe cerebral microvascular endothelial cells-D3 and lung endothelial cells both from human were cultured separately and challenged with P. falciparum field isolates taken directly from malaria patients or 3D7 strain (in vitro maintained culture). The capacity of these P. falciparum isolates to induce endothelial cell apoptosis via cytoadherence or not was then assessed.ResultsOverall, 27 P. falciparum isolates were collected from patients with uncomplicated malaria (n = 25) or severe malaria (n = 2). About half the isolates (n = 17) were able to bind brain endothelial cells (12 isolates, 44%) or lung endothelial cells (17 isolates, 63%) or both (12 isolates, 44%). Sixteen (59%) of the 27 isolates were apoptogenic for brain and/or lung endothelial cells. The apoptosis stimulus could be cytoadherence, direct cell-cell contact without cytoadherence, or diffusible soluble factors. While some of the apoptogenic isolates used two stimuli (direct contact with or without cytoadherence, plus soluble factors) to induce apoptosis, others used only one. Among the 16 apoptogenic isolates, eight specifically targeted brain endothelial cells, one lung endothelial cells, and seven both.ConclusionThese results indicate that the brain microvascular cell line was more susceptible to apoptosis triggered by P. falciparum than the primary pulmonary endothelial cells and may have relevance to host-parasite interaction.
Highlights
Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria
Using cocultured human lung endothelial cell (EC) (HLEC) and parasitized red blood cell (pRBC) field isolates from Gabon, we showed that almost all isolates provoked cytoadherence, only a few triggered apoptosis, and that these isolates tended to have been drawn from patients with neurological disorders [9]
P. falciparum isolates were collected from 25 patients with uncomplicated malaria and 2 patients with severe malaria (1 with convulsions, 1 with prostration)
Summary
Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of malaria remain elusive. Plasmodium falciparum malaria is a life-threatening parasitic disease that kills some half a million people each year, mostly children living in sub-Saharan Africa. The outcome of the infection, which may be asymptomatic, symptomatic, or life-threatening, is known to be influenced by parasite, host, environmental and socioeconomic factors [1]. In Gabon, respiratory distress and cerebral malaria represent, respectively 31% and 24% of severe falciparum in children [2]. A combination of the parasitized red blood cell (pRBC) binding (cytoadhesion, agglutination and rosetting), the host environmental and inflammatory response, endothelial cell (EC) activation, and altered hemostasis can lead to blood pulmonary/brain barrier impairment [3]. It has been demonstrated that pRBC-EC adherence induces caspase 8, 9 and 3 activation, EC apoptosis, and modulates EC expression of TNF-α superfamily genes (Fas, Fas L, DR-6) and apoptosisrelated genes (Bad, Bax, Caspase-3, SARP 2, DFF45/ ICAD, IFN-γ Receptor 2, Bcl-w, Bik and iNOS) [6]. pRBC-EC adherence leads to microvessels blockage, hypoxia, proinflammatory cytokine secretion [6,7,8,9], EC junction modifications, and EC barrier permeabilization [8, 10, 11]
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